Evidence map›Paper›PMID 34516571›Full record

ArticlePLoS pathogens2021

Host phospholipid peroxidation fuels ExoU-dependent cell necrosis and supports Pseudomonas aeruginosa-driven pathology.

Salimata Bagayoko, Stephen Adonai Leon-Icaza, Miriam Pinilla, Audrey Hessel, Karin Santoni, David Péricat, Pierre-Jean Bordignon, Flavie Moreau, Elif Eren, Aurélien Boyancé and 15 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.1field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 22 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Review
  6. CombattingAntibiotics (Basel, Switzerland) · 2025
    Review
  7. Journal of fungi (Basel, Switzerland) · 2025
    Article
  8. Article
  9. Model systems to studyFrontiers in cellular and infection microbiology · 2025
    Review
  10. Review
  11. Article
  12. Cell lipid biology in infections: an overview.Frontiers in cellular and infection microbiology · 2023
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Roles of Two-Component Systems inInternational journal of molecular sciences · 2021
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors at 4 institutions in 3 countries.

Salimata BagayokoInstitute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, Toulouse, France.
Stephen Adonai Leon-IcazaInstitute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, Toulouse, France.ORCID 0000-0002-7546-8228
Miriam PinillaInstitute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, Toulouse, France.ORCID 0000-0003-4317-7706
Audrey HesselInstitute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, Toulouse, France.ORCID 0000-0002-3489-4474
Karin SantoniInstitute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, Toulouse, France.
David PéricatInstitute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, Toulouse, France.
Pierre-Jean BordignonInstitute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, Toulouse, France.ORCID 0000-0003-4073-8117
Flavie MoreauInstitute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, Toulouse, France.
Elif ErenInstitute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, Toulouse, France.
Aurélien BoyancéInstitute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, Toulouse, France.
Emmanuelle NaserInstitute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, Toulouse, France.
Lise LefèvreRESTORE institute, University of Toulouse, CNRS, Toulouse, France.
Céline BerroneInstitute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, Toulouse, France.
Nino IakobachviliDivision of Nanoscopy, Maastricht Multimodal Molecular Imaging Institute, Maastricht University, Maastricht, The Netherlands.ORCID 0000-0003-0797-2665
Arnaud MetaisInstitute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, Toulouse, France.
Yoann RomboutsInstitute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, Toulouse, France.ORCID 0000-0003-4482-2199
Geanncarlo Lugo-VillarinoInstitute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, Toulouse, France.ORCID 0000-0003-4620-8491
Agnès CosteRESTORE institute, University of Toulouse, CNRS, Toulouse, France.
Ina AttréeUniv. Grenoble Alpes, CNRS, CEA, IBS, Bacterial Pathogenesis and Cellular Responses, Grenoble, France.ORCID 0000-0002-2580-764X
Dara W FrankDepartment of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
Hans CleversOncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center, Utrecht, Netherlands.
Peter J PetersDivision of Nanoscopy, Maastricht Multimodal Molecular Imaging Institute, Maastricht University, Maastricht, The Netherlands.ORCID 0000-0002-2964-5684
Céline CougouleInstitute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, Toulouse, France.ORCID 0000-0002-6795-5448
Rémi PlanèsInstitute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, Toulouse, France.
Etienne MeunierInstitute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, Toulouse, France.ORCID 0000-0002-3651-4877
Centre National de la Recherche Scientifique · FRMaastricht University · NLMedical College of Wisconsin · USRoyal Netherlands Academy of Arts and Sciences · NL

Funding

Type III effector-cofactor dynamics within the cellular environmentR01AI104922 · NIAID · MEDICAL COLLEGE OF WISCONSIN · PI FEIX, JIMMY, FRANK, DARA W. · 2013 to 2021
$3.7M
NIAID NIH HHS R01 AI104922
6 · The paper itself

Abstract

Regulated cell necrosis supports immune and anti-infectious strategies of the body; however, dysregulation of these processes drives pathological organ damage. Pseudomonas aeruginosa expresses a phospholipase, ExoU that triggers pathological host cell necrosis through a poorly characterized pathway. Here, we investigated the molecular and cellular mechanisms of ExoU-mediated necrosis. We show that cellular peroxidised phospholipids enhance ExoU phospholipase activity, which drives necrosis of immune and non-immune cells. Conversely, both the endogenous lipid peroxidation regulator GPX4 and the pharmacological inhibition of lipid peroxidation delay ExoU-dependent cell necrosis and improve bacterial elimination in vitro and in vivo. Our findings also pertain to the ExoU-related phospholipase from the bacterial pathogen Burkholderia thailandensis, suggesting that exploitation of peroxidised phospholipids might be a conserved virulence mechanism among various microbial phospholipases. Overall, our results identify an original lipid peroxidation-based virulence mechanism as a strong contributor of microbial phospholipase-driven pathology.

Indexed as

AnimalsBacterial ProteinsHost-Pathogen InteractionsHumansLipid PeroxidationMiceMice, KnockoutNecrosisPseudomonas aeruginosaPseudomonas InfectionsVirulenceBacterial Proteinspseudomonas exoprotein A protein, Pseudomonas aeruginosa

Identifiers

PMID34516571
PMCPMC8460005
OpenAlexW3199248154

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.